Not Applicable
Not Applicable
This invention relates to the field of eye protection and vision enhancement by filters of UV and the higher energy visible (HEV) lightxe2x80x94such as sunglass lenses. More specifically, it relates to the use of the polymerization product resulting from the oxidation of 3-Hydroxykynurenine (3-OHKyn), as a light filtering component or dye to achieve such eye protection and vision enhancement in a variety of products including sunglass lenses, and ophthalmic lenses in general, windows, light filters such as photograph covers, packaging material, canopies, etc., and other similar media utilized to protect valuable goods from radiation damage.
Reference has been made previously to optical filters that mimic the yellow pigment of the human ocular lens by a) Parties associated with the product xe2x80x9cAcrySofNatural IOLsxe2x80x9d and found on the internet web site: http://www.eyeworld.org/aug02/0802p30.html, and by b) Gallas on the concept of the current patent application and made in the form of a Disclosure document deposit to the PTO.
Over the last decade, scientific research has underscored the threat posed by both UV light to the ocular lens, and HEV (high energy visible) light to the retina. And recently, an increasing appreciation for the importance of HEV light reduction has occurred within the ophthalmic industry. Lenses that reduce or eliminate HEV (mainly the blue and violet) light generally cause the wearer to experience increased contrast and visual acuity. Such lenses also offer more protection to the retina against diseases that have a photooxidative basis. However, such lenses often cause distortions in color and loss of proper color perception.
It is known that the human crystalline lens yellows with age and even turns brown, along with the occurrence of cataracts. Because the presence of cataracts impedes the vision process due to excessive light scatter and glare from fluorescence, the aged, cataract lens is removed and replaced with a clear lens. However, the yellow-brown coloration reduces primarily the HEV (high energy visible) light; thus, it should also provide the same vision-enhancing benefits as the dyes used in other HEV-reducing sun lenses. This protective feature of the crystalline lens is illustrated in FIG. 1. (taken from Weale R A: Age and the transmittance of the human crystalline lens. J Physiol 395:577-587, 1988.)
But because both the cataract and the yellow-brown pigment occur with age, the vision-protecting and vision-enhancing benefits of the yellow-brown pigment are masked by the vision-impeding aspects of the cataract. This is unfortunate because there are significant vision benefits that can be associated with the yellow-brown ocular pigment of the crystalline lens.
First, it should be expected that the neuro-physiology of the eye must be completely compatible with the optical properties of this pigmentxe2x80x94and specifically its transmission spectrum, and that minimal loss of color perception should thus occur from any filter that utilizes it. This yellow-brown filter should also be expected to offer protection to the retina by reducing the intensity of the HEV light and thus reducing the risks of age-related macular degeneration (AMD).
In practice, this protective coloration occurs after the retina has already been exposed to damaging sunlight for many years of a person""s childhood and early adult life. And, in the case of senior citizens who undergo operations to remove the cataract lens, a clear plastic lens is used as the replacement. This occurs, unfortunately, at a time of their lives when the antioxidant capacity of their retina is seriously compromised; and the increased dose of HEV light, that is now able to reach the retina, therefore increases the risk of retinal damage (AMS).
However, it is possible to synthesize the yellow pigment of the human crystalline lens in vitro, and which has a transmission spectrum identical to that of the material synthesized in vivo. Such an in vitro-synthesized lens pigment (hereinafter referred to as SLP), used in an optical filter, such as a sun lens, would therefore provide the same protection to the eye from sunlight damage, and the same contrast enhancement and color perception-preserving qualities as the natural, yellow-to-brown pigment produced in vivo by the ocular lens.
The molecule that is responsible for the yellow-to-brown coloration of the crystalline lens has been identified as the oxidative polymerization product of 3-Hydroxykynurenine (3-OHKyn). Thus, it has been shown that a synthetic version of the yellow pigment of the human ocular lens, SLP, can be made in vitro by the auto-oxidation by the same precursor, 3-OHKyn, in aqueous media.
The auto-oxidation of (3-OHKyn) in water has bee described elsewhere (Garner, B., D C Shaw, R A Lindner, J A Carver, and R J Truscott, Non-oxidative modification of lens crystallins by kynurenine: novel post-translational protein modification with possible relevance to ageing and cataract. Biochimica et Biophsica Acta. 1476(2):265-78, 2000), and is summarized as follows:
Auto-oxidation, or polymerization of 3-Hydroxykynurenine (3-OHKyn) proceeds by dissolving 3-OHKyn in water and then bubbling air into the stirred solution, after raising the pH to a value of about 8. The darkness and degree of brownness can be controlled by the concentration of precursor monomer and polymerization conditions that favor the degree of oxidationxe2x80x94like higher values of the pH, temperature and incubation time.
As a specific example, a) 2.5 grams of 3-Hydroxykynurenine were dissolved in IL of de-ionized water, b) 0.07 g of ferric chloride, FeCl3, was dissolved in 250 cc of de-ionized water; and c) 6.1 g of potassium persulphate were dissolved in 250 cc of de-ionized water; then a), b) and c) were each heated to 50 degrees C.; then solution b) was added to a) to produce solution d) and stirred; then solution c) was added to d) drop-wise over a period of 5 minutes and the final solution was allowed to stir, under a condenser, at 50 degrees C. for 24 hours. The product, SLP, was a concentrated black solution e). The synthesis product was then purified as follows: 200 cc of a dilute solution of aqueous sulphuric acid was added to e) bringing the pH of the solution e) to a value of 1.5. and a final volume of 1700 cc. The solution was allowed to incubate without stirring for 24 hours. This caused the black polymerization product to aggregate and settle to the bottom of the vessel. Then 1.3 L of the clear, lightly colored supernatant was poured off. This supernatant contains water-soluble, small oligomers of the product as well as un-reacted monomer and the synthesis reagents and salts. An additional 1.3 of fresh de-ionized and acidified water was added and stirred with the remaining 0.4 L of solution to give, again, a 1.7 L solution at pH 1.5. This solution was allowed to incubate unstirred for an additional 24 hours and 1.3 L of the lightly-colored supernatant was poured off.
The aqueous product was able to be re-suspended and solubilized by readjusting the pH to 8 with the addition of 100 cc of a dilute solution of aqueous sodium hydroxide; and it was able to be dispersed well in its acidified form by mixing with tetraydrofuran as is described later in this paper. A small aliquot of this solution was found to have 3 mg of the synthetic ocular lens pigment (SLP) per mL of water. This aqueous solution is referred hereinafter as the xe2x80x9cstock solution.xe2x80x9d
A less concentrated solution for optical measurements was prepared by adding 1 ml of the stock solution to 2 ml of water to give a concentration of 1 mg/ml. The diluted solution of the yellow pigment was then injected into a cuvette with 1 cm path length and placed into the sample compartment of a recording UV-Visible spectrophotometer. The transmission spectra is shown in FIG. 2.
The invention proposed here is to incorporate, into plastic and glass optical lenses, and other light filters, a synthetic version of the same material found in the human crystalline lens, the polymerization product of 3-OHKyn, and responsible for the optical transmission spectrum of the crystalline lens. This material is hereafter referred to as the xe2x80x9csynthetic lens pigment,xe2x80x9d or xe2x80x9cSLP,xe2x80x9d and its precursor referred to as 3-OHKyn. Because this material always occurs in an aqueous environmentxe2x80x94and indeed, its surface structure is presumed to be hydrophilicxe2x80x94it will be necessary to convert the surface of the molecular structure to one that is hydrophobic in order for the final synthetic material to disperse well into most of the liquid plastic resins and monomers that are typically used in ophthalmic devices. This enhanced dispersibility reduces objectionable light scatter and haze in the final ophthalmic lens or light filter product. After purification, the material can be combined with liquid plastic resin in a thermoset casting process or in a thermoplastic, injection molding process where the yellow-to-brown pigment powder or liquid is evenly dispersed in the plastic to form sunglass lenses and other plastic light filters. At least one example of a hydrophilic plastic application will be provided.
Advantages of the Invention: Such a sunglass lens should offer very good protection to the retina and ocular lens while not disturbing color perception. While reduction of high energy visible (HEV) light offers increased protection to the retina, there is a chance that a reduction of the violet and blue colors may disturb the perception of color when people use such sunglass lenses. This loss of color perception is less likely to occur with lenses made with SLP because the optical transmission of such lenses closely match the transmission of the actual human lensxe2x80x94for which the neuro-physiology of the eye-brain system is well-adapted. Use of the polymerization precursor, 30 HKyn, that is actually used in the in vivo polymerization synthesis should give the best representation of the optical transmission spectrum of the naturally-occurring ocular pigment.
While it is possible to mimic the transmission spectrum of SLP with artificial dyes, there are several disadvantages to doing this:
1. Small differences between the transmission spectrum of SLP and the simulated one achieved by combining artificial dyes lead to significant differences in the color perception when using such lenses on tests like the Farnsworth-Munsell color test. If the act of mimicking the transmission spectrum is left to the optician or optometrist, it is very likely that these differences will not be appreciated;
2. Because several artificial dyes will be needed in order to better mimic the SLP transmission spectrum, they will fade at different rates when exposed to sunlight after time. This will cause the transmission spectra to differ even more.